Demencias no Alzheimer
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Este documento presenta una revisión de las demencias no Alzheimer, incluyendo demencias de inicio en edad pre-senil como la demencia fronto-temporal, la demencia con cuerpos de Lewy y la afasia progresiva no fluente. Se describen casos clínicos ilustrativos de cada tipo de demencia y sus hallazgos de neuroimagen e neuropsicológicos. Además, se discute la prevalencia y presentación clínica de estas demencias, haciendo énfasis en la necesidad de un mejor reconocimiento de las mismas.
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Demencias no Alzheimer
- 1. Evaluación clínica de las demencias no Alzheimer XXIV Congreso Peruano de Radiología Sociedad Peruana de Radiología 25 Octubre 2014, Lima-Perú Nilton Custodio Instituto Peruano de Neurociencias ncustodio@ipn.pe
- 2. Agenda • Algunas demencias no son enfermedad de Alzheimer. • Demencias de inicio en edad pre-senil. • El amplio espectro de la demencia fronto-temporal (DFT). • Parkinsonismo y demencia con cuerpos de Lewy. • El plan de trabajo en demencias no Alzheimer.
- 3. Agenda • Algunas demencias no son enfermedad de Alzheimer. • Demencias de inicio en edad pre-senil. • El amplio espectro de la demencia fronto-temporal (DFT). • Parkinsonismo y demencia con cuerpos de Lewy. • El plan de trabajo en demencias no Alzheimer.
- 4. IRM en “síntomas visuales complejos” en 2011
- 5. IRM en “síntomas visuales complejos” en 2011
- 6. IRM en “síntomas visuales complejos” en 2013
- 7. IRM en “síntomas visuales complejos” en 2013
- 8. “Síntomas visuales complejos” y atrofia progresiva a nivel posterior
- 9. “Síntomas visuales” en mujer senil joven con diagnóstico clínico de Atrofia Cortical Posterior (ACP) • F, 57, izquierda. Secretaria ejecutiva bilingüe. SV hace 6 años. • Inicia con dificultades para identificar objetos delante de ella. Con frecuencia, ella se “golpea el hombro al dar la vuelta en una esquina antes de tiempo”. • Dificultad para la lectura: Primero, “lee en desorden, porque se salta los renglones”, y luego “las letras saltan de un lado a otro” cuando intenta leer un letrero. • Hace un año, se agrega dificultad para reconocer escenarios habituales a los que acude: supermercado, centro comercial o el auto del esposo.
- 10. Evaluación neuropsicológica en casos limeños de ACP Caso 1 Caso 3
- 11. Evaluación neuropsicológica en casos limeños de ACP
- 12. IRM en un paciente con “agramatismo”
- 13. IRM en un paciente con “agramatismo”
- 14. “Agramatismo” en un paciente pre-senil con afasia progresiva no fluente (APNF) • M, 54, diestra. Auxiliar administrativo en Luz del Sur. TE: 3 años. • Paciente en el inicio, se comunica con oraciones cortas simples, y con errores gramaticales (produce oraciones con palabras de contenido-sustantivos y verbos; pero omite o sustituye las palabras de función-artículos y preposiciones). • Dos años después, se agrega anomia, parafasia fonémica y dificultad para entender órdenes complejas. • 6 meses antes de la evaluación, dificultad para entender lo que lee.
- 15. APNF y lámina de descripción de Boston Yo… no sé,….. solamente loza, loza, agua, agua ….… solamente en el quiosco, espera……….un poquito lavar ……….loza,……. muy bien, agua, agua…”
- 16. APNF y comprensión de oraciones • Simples • Complejas
- 17. IRM en un policía pre-senil con anomia
- 18. IRM en un policía pre-senil con anomia
- 19. “Anomia” del policía pre-senil con demencia semántica • M, 53, diestra. Teniente-coronel PNP. TE: 4 años. • Paciente inicia con dificultad para referirse a los objetos comunes de la oficina y de casa, por lo que él trata de explicar las características de los objetos, tornándose “verborreico” y luego irritable; diagnosticado como depresión, indican sertralina y risperidona. • Dos años después, se torna “poco comunicativo”, con lenguaje vacío de contenido, con frecuencia utiliza palabras como “eso”, “esto” entre otras. • 1 año antes de la evaluación, además no puede leer y errores en escritura.
- 20. Demencia semántica y lámina de Boston A ver... Se cayó... Se va a cayendo, para que no se caiga... ¿no lo ves? (,señalando el piso). Se cambió la llave... (señala agua) y se voltea... Y está lavándose el plato, arriba... Está la llave abierta ¿no?. ¡Eso nomás!... Y la llave, y el gimnasio, cae de allá (señala galletas), girando la banca... ¿entiendes?
- 21. Serios problemas en la denominación Es un animal……….. Un tipo de caballo…………. Caballo con rayas…………………
- 22. Serios problemas en la comprensión del lenguaje Falla en tareas de emparejamiento palabra-dibujo
- 23. Falla en tareas de asociación semántica
- 24. Agenda • Algunas demencias no son enfermedad de Alzheimer. • Demencias de inicio en edad pre-senil. • El amplio espectro de la demencia fronto-temporal (DFT). • Parkinsonismo y demencia con cuerpos de Lewy. • El plan de trabajo en demencias no Alzheimer.
- 25. Prevalencia de demencia de inicio en edad pre-senil Hombres: 78.2 casos por 100 000 Mujeres: 56.4 casos por 100 000 Harvey R. Dementia Research Group 1998
- 26. Distribución de tipos de demencia por grupo de edad Demencia de inicio antes de 65 Demencia de inicio después de 65 Jefferies K, Agrawal N. Adv Psychiatry Treat 2009;15:380-388
- 27. En LA no tenemos estudios en poblaciones de menos de 65 años de edad
- 28. El metabolismo anormal de ciertas proteínas genera cuerpos de inclusión con cierto fenotipo neurodegenerativo Genética y Ambiente Metabolismo Anormal Proteína Vulnerabilidad Celular Selectiva Disfunción Sistema Neural Fenotipo Clínico Colinérgica Serotoninérgica Noradrenérgica Dopaminérgica Cuerpos Pick Cuerpos Lewy Placas neuríticas Ovillos NF Circuitos F-SC Hipocampo-CA Proyecciones TC-SL
- 29. Estas proteínas generan más del 75% de demencias de inicio tardío y casi el 100% de demencias de inicio precoz • Proteína Tau • Degeneración fronto-temporal, enfermedad de Alzheimer, parálisis supranuclear progresiva, degeneración cortico-basal. • Proteína alfa-Sinucleína • Enfermedad de Parkinson, demencia con cuerpos de Lewy, Atrofia multisistémica • Proteína Beta-Amiloide • Enfermedad de Alzheimer, síndrome de Down • Prionopatía: Enfermedad Creutzfeld-Jacob y variantes. • Desorden de nucleótidos repetidos: Enfermedad de Huntington y ataxias espinocerebelosas.
- 30. La afectación específica del circuito define los síntomas cognitivos y los SPCD en enfermedades neurodegenerativas Degeneración Fronto-Temporal Sistema Frontal-SubCortical Disfunción Ejecutiva Desinhibición Apatía Enfermedad Parkinson Demencia con C. Lewy Sistema Dopaminérgico Sistema Límbico Transtorno en atención Habilidad visuoespacial Depresión Desórdenes del sueño Alucinaciones Enfermedad de Alzheimer Hipocampo y Corteza de Asociación Amnesia Afasia Psicosis Apatía Depresión Tau Cuerpo Pick Tau ONF Amiloide PN Sinucleína Cuerpo Lewy
- 31. DFT es más frecuente de lo que pensamos Lugar de estudio Casos (n) Definición de caso Estimado por 100,000 en 45–64 años de edad 95 % CI Zuid-Holland, Holanda (Rosso et al. 2003) 55 DFTvc 4.0 2.8 – 5.7 Cambridgeshire, UK (Ratnavalli et al. 2002) 11 DFTvc + APP 15 8.4 – 27.0 London, UK (Harvey et al. 2003) 18 DFTvc 15.4 9.1 – 24.3 Brescia, Italia (Borroni et al. 2010) 213 DFTvc + APP 22 17 – 27 Ibaraki, Japon (Ikejima et al. 2009) 17 DFTvc 2.0 1.3 – 3.2 Knopman D, Roberts R. J Mol Neurosc 2011;45:330-335
- 32. DFT después de los 65, es rara en frecuencia? 22/100,000 78/100,000 54/100,000 n=108 n=97 n=21 Borroni B, et al. J Alzheimers Dis 2010;19:111-116
- 33. Agenda • Algunas demencias no son enfermedad de Alzheimer. • Demencias de inicio en edad pre-senil. • El amplio espectro de la demencia fronto-temporal (DFT). • Parkinsonismo y demencia con cuerpos de Lewy. • El plan de trabajo en demencias no Alzheimer.
- 34. Degeneración fronto-temporal, demencia fronto-temporal “Enfermedad de Pick” o “complejo de Pick”? Enfermedad de Pick • Europa: Diagnóstico clínico, con o sin cuerpos de Pick en la patología. • América: Diagnóstico patológico, independiente de presentación clínica. Complejo de Pick DCB PSP APP DFTvc DFT-ELA
- 35. El amplio espectro clínico de DFT Cambios precoces y progresivos del comportamiento y/o deterioro del lenguaje Predominio de síntomas conductuales Predominio de compromiso del lenguaje: APP DFT conductual Afasia Progresiva no fluente Demencia Semántica Afasia Logopénica
- 36. Los síntomas iniciales en DFTvc no afectan memoria
- 37. Los síntomas iniciales en DFTvc son similares a enfermedades psiquiátricas • Desorden bipolar • Psicosis de inicio tardío • Desorden de la personalidad • Cambios de personalidad relacionados a edad • Desorden obsesivo-compulsivo • Abuso de alcohol • Depresión atípica • Trastorno por déficit de atención/hiperactividad
- 38. En DFTvc, los síntomas iniciales no son reconocidos tempranamente
- 39. En estadios iniciales de DFTvc, una relativa preservación de la memoria episódica
- 40. Rendimiento en atención, memoria y lenguaje en pacientes con EA, DFTvc y controles de Clínica Internacional Dominio Cognitivo Control (n=60) EA (n=60) DFTvc(n=32) p Atención Dígitos hacia adelante 5.16 (2.4) 3.3 (1.7) 3.5 (1.2) < .001*† TMT-A (s) 41.2 (13.6) 59.4 (14.7) 69.8 (16.5) < .01*† ‡ Memoria Recuerdo inmediato 24.9 (8.6) 11.3 (3.5) 17.4 (4.7) < .001*† ‡ Recuerdo retrasado 20.6 (7.9) 7.3 (2.5) 10.6 (3.6) < .001*† ‡ Reconocimiento 16.9 (3.1) 4.9 (3.6) 13.3 (2.4) < .001*† ‡ Lenguaje Denominación de Boston 18.6 (0.5) 13.6 (1.6) 15.2 (1.5) < .001*† Fluencia semántica 18.5 (1.2) 11.7 (2.1) 12.3 (2.5) < .001*† * Control vs. EA † Control vs. DFT ‡ EA vs DFT Custodio N, et al. Rev NeuroPsiquiatría 2012;75(4):120-128
- 41. En estadios iniciales, marcado compromiso de las funciones ejecutivas 1. Orbito-frontal 2. Dorso-lateral 3. Ventro-medial 4. Cíngulo anterior CPF Dorsolateral Núcleo Caudado Globus Pallidus Tálamo
- 42. Rendimiento en funciones viso-espaciales y ejecutivas en pacientes con EA, DFTvc y controles de Clínica Internacional Dominio Cognitivo Control (n=60) EA (n=60) DFTvc(n=32) p Viso-espacial/Constructivo Copia de dibujos 10.9 (1.6) 4.6 (3.1) 8.5 (3.2) < .001*† ‡ Test de cubos (WAIS III) 11.8 (1.7) 4.5 (3.4) 6.7 (2.1) < .001*† ‡ Función Ejecutiva (Clásica) Dígitos hacia atrás 4.8 (1.1) 3.2 (1.6) 3.9 (1.2) < .01*† Fluencia fonológica 16.4 (4.9) 12.3 (3.4) 11.3 (4.2) 0.05*† TMT-B (s) 96.6 (35.3) 145 (58.7) 178.7 (42.2) < .001*† ‡ WCST (puntaje total) 5.3 (0.6) 3.1 (1.4) 3.2 (1.3) < .01*† WCST (perseverancia) 2.1 (1.2) 4.5 (2.3) 9.5 (5.3) < .01*† ‡ * Control vs. EA † Control vs. DFT ‡ EA vs DFT Custodio N, et al. Rev NeuroPsiquiatría 2012;75(4):120-128
- 43. DFT conductual Posible: 3 de los siguientes criterios A. Inicio temprano de desinhibición conductual . B. Inicio temprano de apatía o inercia. C. Inicio temprano de pérdida de simpatía o empatía. D. Inicio temprano de conducta perseverante, estereotipada o compulsiva/ritualista. E. Hiperoralidad y cambios en la dieta. F. Perfil neuropsicológico: Déficit ejecutivo con relativa preservación de las funciones de memoria y visuo-espaciales. Rascovsky K, et al. Brain 2011;134:2456-2477.
- 44. DFT conductual Probable: Criterios A,B y C A. Criterios para DFT posible. B. Declinación funcional significativa (reportado por el cuidador, o evidenciado por CDR, o cuestionario de actividades funcionales). C. Una de las imágenes cerebrales compatibles con DFT conductual: 1. Atrofia frontal y/o temporal anterior en IRM o TC 2. Hipo-perfusión o hipo-metabolismo frontal y/o temporal anterior en PET o SPECT. Rascovsky K, et al. Brain 2011;134:2456-2477.
- 45. IRM en DFT conductual Ravinovici GD, Miller BL. CNS Drugs 2010;24(5):375-398.
- 46. DFT conductual definitivo A. Criterios para DFT conductual probable o posible. B. Evidencia en la biopsia cerebral o post-morten. C. Presencia de mutación patogénica conocida. Criterios de exclusión de DFT conductual A. Desorden médico o SNC no degenerativo. B. Desorden conductual explicado por enfermedad psiquiátrica. C. Biomarcadores positivos para EA. Rascovsky K, et al. Brain 2011;134:2456-2477.
- 47. Agenda • Algunas demencias no son enfermedad de Alzheimer. • Demencias de inicio en edad pre-senil. • El amplio espectro de la demencia fronto-temporal (DFT). • Parkinsonismo y demencia con cuerpos de Lewy. • El plan de trabajo en demencias no Alzheimer.
- 48. Neuropatología de la enfermedad de Parkinson Patología de la Sustancia negra Pérdida neuronal Inclusiones Lewy
- 49. Neuropatología de la enfermedad de Parkinson Patología de la α-sinucleína Sustancia negra Corteza cerebral
- 50. Estadio del depósito de cuerpos de Lewy según Braak Braak H, et al. J Neurology. 2002;249(suppl 3):1432-1459.
- 51. Demencia de la enfermedad de Parkinson y demencia con cuerpos de Lewy una misma enfermedad? α-Sinucleína Cuerpos Lewy α-Sinucleína Cuerpos Lewy α-Sinucleína Cuerpos Lewy • Localización de los cuerpos de Lewy. Enfermedad Parkinson Demencia enfermedad Parkinson Demencia con cuerpos Lewy Parkinson Plus Ss motores enfermedad Parkinson Demencia cuerpos Lewy • Criterios arbitrario del año del inicio de síntoma motor o síntoma cognitivo.
- 52. Dos caminos, un destino: demencia con cuerpos de Lewy Síntomas cognitivos Síntomas motores Demencia con Cuerpos de Lewy Patología CL corticales CL tronco cerebral Deficiencia de Dopamina Patología CL cortical Deficiencia ACh cortical Cuadro Clínico Parkinsonismo Cognición fluctuante Alucinaciones Visuales Demencia progresiva Cuadro Clínico Demencia Cognición fluctuante Incremento síntomas NP
- 53. Frecuencia y severidad de SPCD en DCL-EP y DEP según evaluación por NPI en Lima DCL-EP DEP Algún síntoma neuropsiquiátrico 83.3 % 91.3 % NPI ≥ 4 72.2 % 73.9 % NPI Total 12.13 ± 10.76 19.35 ± 20.43 Frecuencia Ansiedad 66.6 % 60.9 % Depresión 66.6 % Alt. Sueño 52.2 % Apatía 55.5 % 47.8 % Severidad Ansiedad 3.96 ± 2.71 Delusiones 4.96 ± 3.74 Apatía 3.56 ± 2.54 4.77 ± 3.49 Irritabilidad 3.21 ± 2.37 Alt. Apetito 4.14 ± 3.28 Alteraciones del sueño 3.16 ± 1.76 4.87 ± 3.71 DCL-EP: Deterioro cognitivo leve-Enfermedad de Parkinson; DEP: Demencia de enfermedad de Parkinson Custodio N, y col. Interciencia 2013;4(3):105-112.
- 54. En un estudio transversal las alucinaciones se presentan en el 34.7 % de pacientes con DEP Custodio N, y col. Interciencia 2013;4(3):105-112.
- 55. La prevalencia de psicosis se incrementa con el tiempo de enfermedad de EP Año de evaluación Psicosis (+) Prevalencia Basal 41/230 18% Año 4 51/142 36% Año 8 45/88 51% Año 12 12/25 48% Acumulado 137/230 60% Forsaa EB, et al. Arch Neurol 2010;67:996-1001.
- 56. Alucinaciones no visuales y síntomas menores son más comunes de lo que pensamos Fénelon G, et al. Mov Disord 2010;25:763-766.
- 57. Continuum de síntomas psicóticos en EP Ilusiones Alucinaciones Desorientación Pensamiento desorganizado Delusiones Agitación verbal y física Menos Severo Más Severo
- 58. Evolución clínica de los sintomas psicóticos en EP • Las supuestas “alucinaciones benignas” son de curso “maligno” – En el seguimiento longitudinal a 3 años, 80% de “alucinaciones benignas” progresan a psicosis más severas1. • 70% pacientes con psicosis, permanecen en ese estado después de 2 años2. • Los pacientes que responden a anti-psicóticos atípicos, presentan “psicosis de rebote” luego de la descontinuación del tratamiento3. 1. Goetz CG , et al. Arch Neurol 2006;63:713-716. 2. Factor SA, et al. Neurology 2003;60:1756-1761. 3. Fernandez HH, et al. Mov Disord 2005;20:104-115
- 59. Criterios clínicos en Demencia con cuerpos de Lewy • Característica central: – Declinación cognitiva progresiva • Característica nuclear: – Cognición fluctuante – Alucinaciones visuales recurrentes – Características espontáneas de Parkinsonismo • Característica de soporte: – Desorden conductual del sueño REM – Sensibilidad a neurolépticos – Disminución en captación DA en ganglios basales en TEP. – Síncope McKeith, et al. Neurology2005;65:1863-1872.
- 60. SPCD en doce casos probables de Demencia con cuerpos de Lewy : HMC – CI (2002-2006) 12 10 8 6 4 2 0 83.3% Alucinaciones Visuales 16.7% Alucinaciones Auditivas 66.6% Delusiones Falsas Identificaciones Depresión Custodio N, y col. XII Congreso Panamericano Neurología 2007. 50% 66.6%
- 61. Agenda • Algunas demencias no son enfermedad de Alzheimer. • Demencias de inicio en edad pre-senil. • El amplio espectro de la demencia fronto-temporal (DFT). • Parkinsonismo y demencia con cuerpos de Lewy. • El plan de trabajo en demencias no Alzheimer.
- 62. Adaptación y validación de pruebas cognitivas breves para evaluación de cribado de demencia
- 63. Fluxograma para evaluación de pacientes mayores de 65 años de edad, con sospecha de “deterioro de memoria”: Visita 0 PFAQ PDR-M MMSE PFAQ N PDR-M N MMSE N PFAQ límite PDR-M N MMSE N PFAQ N PDR-M N MMSE límite PFAQ An PDR-M N MMSE An PFAQ An PDR-M An MMSE An PFAQ An PDR-M An MMSE límite TMAE TCAE ENVEJECIM DCL-Amn T@M Evaluación de “Demencia” ACE + IFS Visita 1
- 64. Visita 1: Evaluación para EA probable V 0 V 1 Cribado Examenes Sangre Medicación prescrita Imágenes cerebrales Descarte depresión Criterios EA probable Hemograma Glucosa Creatinina Electrolitos TGO/TGP VIH VDRL T3/T4/TSH Vitamina B12 Analgésicos opioides “descongestionantes” Anti-espasmódicos Anti-colinérgicos Antidepresivos Antiarritmicos Antipsicóticos Antieméticos Ansiolíticos Valproato Índice de Hachinski
- 65. Addenbrooke´s Cognitive Examination (ACE) puede detectar DFTvc y APP
- 66. Utilidad del ACE en pacientes peruanos con EA y DFT: Características clínico-demográficas Controles (n=40) EA (n=40) DFT (n=18) p Edad (años) 68.9 (4.6) 73.0(4.2) 66.7 (3.9) ˂0.001* ‡ Género (F:M) 23:17 26:14 8:10 0.34 Educación (años) 12.4(2.8) 11.7(2.8) 12.3(2.8) 0.46 ADAScog 3.17(2.8) 21.5(5.8) 19.0(2.4) ˂0.001* † BDI-II 4.88(2.7) 4.35(2.2) 3.00(2.3) 0.30 MMSE 29.1(0.7) 21.2(2.8) 26.7(1.5) ˂0.001* †‡ ACE 93.3(2.6) 67.8(5.0) 76.8(5.5) ˂0.001* †‡ * Control vs EA, p ˂ 0.001 † Control vs DFT, p ˂ 0.001 ‡ EA vs DFT, p ˂ 0.001 Custodio N, et al. Vertex Rev Arg Psiquiat 2012;XXIII:165-172.
- 67. Utilidad del ACE en pacientes peruanos con EA y DFT: Análisis discriminatorios entre pacientes y controles 0.00 0.25 0.50 0.75 1.00 Sensitivity 0.00 0.25 0.50 0.75 1.00 1-Specificity ace ROC area: 01 mmse ROC area: 0.9836 Reference Custodio N, et al. Vertex Rev Arg Psiquiat 2012;XXIII:165-172.
- 68. Utilidad del ACE en pacientes peruanos con EA y DFT: Punto de corte para detectar demencia sugerido es 86 Controles (n=40) EA (n=40) DFT (n=18) MMSE > 27 100 % 0 % 50 % ACE > 90 77.5 % 0 % 0 % ACE > 86* 100 % 0 % 0 % ACE > 80 100 % 0 % 27.8 % El MMSE muestra una baja sensibilidad para pacientes con DFT y el punto ideal de corte para la detección de demencia en el ACE pareciera ser 86/100. Custodio N, et al. Vertex Rev Arg Psiquiat 2012;XXIII:165-172.
- 69. Utilidad del ACE en pacientes peruanos con EA y DFT: Evaluación de los subdominios del ACE Dominio cognitivo EA DFT p Orientación 5.75 (0.9) 8.89 (0.7) ˂ 0.001 Atención 5.98 (0.8) 5.83 (0.8) 0.52 Memoria Total 14.1 (1.7) 20.90 (3.2) ˂ 0.001 Fluencia verbal 5.45 (0.9) 4.94 (0.6) ˂ 0.001 Lenguaje 22.0 (1.7) 17.4 (0.9) ˂ 0.001 Habilidad visuo-espacial 1.33 (0.9) 2.56 (1.0) ˂ 0.001 VLOM 4.53 (0.8) 2.08 (0.1) ˂ 0.001 Custodio N, et al. Vertex Rev Arg Psiquiat 2012;XXIII:165-172.
- 70. La capacidad discriminatoria de IFS fue superior a FAB para detectar demencia Controles: 46 EA L-M: 35 DFT:34 Punto Corte Demencia Sensibilidad Especificidad IFS (23.5/30) 97.1 % 97.9% FAB (14.5/18) 81.1% 97.9% Custodio N, et al in preparation
- 71. La capacidad discriminatoria de IFS fue superior Controles: 46 EA L-M: 35 DFT:34 Punto de corte DFT Sensibilidad Especificidad IFS (17.5/30) 94.1 % 94.2% FAB (13.0/18) 82.3% 48.5% Custodio N, et al in preparation a FAB para detectar DFT
- 72. Fluxograma para evaluación de pacientes menores de 65, con “deterioro cognitivo” o “síntomas conductuales”: Visita 0 PFAQ PDR-M MMSE PFAQ N PDR-M N MMSE N PFAQ límite PDR-M N MMSE N PFAQ N PDR-M N MMSE límite PFAQ An PDR-M N MMSE An PFAQ An PDR-M An MMSE An PFAQ An PDR-M An MMSE límite DCL- No Amn Evaluación de “Demencia” Visita 1 ACE + IFS Evaluación Neuropsicológica especializada
- 73. Visita 1: Evaluación para DFT probable Analgésicos opioides “descongestionantes” Anti-espasmódicos V 0 V 1 Cribado Examenes Sangre Medicación prescrita Imágenes cerebrales Evaluación Neuropsicológica Criterios DFT probable Hemograma Glucosa Creatinina Electrolitos TGO/TGP VIH VDRL T3/T4/TSH Vitamina B12 Anti-colinérgicos Antidepresivos Antiarritmicos Antipsicóticos Antieméticos Ansiolíticos Valproato Índice de Hachinski Evaluación Psiquiátrica Frontotemporal Dementia Rating Scale PL genética
- 74. Demencias no Alzheimer: Conclusiones • Las DNA, son más frecuentes en etapas pre-seniles. • Los síntomas tempranos predicen la localización anatómica. • Compromiso de memoria no es un síntoma cardinal en DNA. • Trastornos de conducta y del lenguaje, sugieren DFT. • Parkinsonismo y síntomas psicóticos, sugieren demencia con cuerpos de Lewy. • La evaluación neuropsicológica y las neuro-imágenes son útiles para confirmar la hipótesis diagnostica. • Un adecuado plan de trabajo con pruebas de cribado validadas permite detectar eficazmente DNA.
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Notas del editor
- Of the five studies of the prevalence of CS-FTLD, four were from Western Europe and one was from Japan. Three of the four European studies used the 1998 diagnostic criteria (Neary et al. 1998). The London, UK, and Ibaraki, Japan studies used the original Lund– Manchester criteria (The Lund and Manchester Groups 1994) which did not explicitly recognize PPA. Three studies examined only bvFTD (Rosso et al. 2003; Harvey et al. 2003; Ikejima et al. 2009). Prevalence estimates from these three studies ranged from 2 to 15.4 per 100,000 persons in the 45–64-year-old age range. In the two studies that identified both syndromes (Ratnavalli et al. 2002; Borroni et al. 2010), the point estimates of prevalence were 15 and 22 cases per 100,000 in the 45–64-year-old age range. The incidence estimates for CS-FTLD were clustered in a tight range, but the prevalence estimates differed by a factor of 10. We believe that the low estimates of prevalence (Rosso et al. 2003; Ikejima et al. 2009) resulted from insensitive diagnostic criteria and inadequate recognition. Indeed, the studies that reported lower prevalence estimates were ones that used the older 1994 criteria (The Lund and Manchester Groups 1994). It is possible that the very high estimates of prevalence in persons over age 65 years in some studies (Borroni et al. 2010; Garre-Olmo et al. 2010) do not reflect neuropathological FTLD and therefore represent an overdiagnosis of bvFTD. Neuropathological studies typified by the large multicenter study (Rascovsky et al. 2011) simply do not support the contention that most FTLDs occur in persons over age 65. Based on the best available data, we believe that the most plausible figures are that roughly 60% of CS-FTLD occurs in the 45–64-year-old age range, and that the prevalence of CSFTLD is 15–22 per 100,000 in that age range. Because of the rarity of PPA and bvFTD, none of the studies reviewed here employed active case detection methods. Instead, they all relied on passive surveillance and case detection by medical record review. The basis for claiming that a prevalence or incidence could be calculated was that each study was able to define a geographic catchment area for their case review and claim that any case of FTLD in a resident of the catchment region that was diagnosed would have been captured by their methodology. The main threat to the validity of these observations is the accuracy of clinical diagnoses. Undercounting of cases is a distinct possibility because the clinical detection of bvFTD or PPA requires a level of expertise in behavioral neurology that is possessed by few neurologists and even fewer non-neurologists. We believe that the very low estimate of CS-FTLD prevalence from Ibaraki, Japan (Ikejima et al. 2009) reflected the use of insensitive diagnostic criteria for, and, simultaneously, a limited awareness of, the clinical syndromes of FTLD in the practitioners in Ibaraki. Overdiagnosis and misclassification of bvFTD or PPA are also possible and could occur if some of the cases that were labeled clinically as bvFTD or PPA were actually due to the pathology of Alzheimer’s disease, Lewy body disease, or cerebrovascular disease. A number of the behavioral features of bvFTD may occur in the dementia of AD or in dementia with Lewy bodies. AD pathology sometimes occurs in persons diagnosed clinically with bvFTD or PPA (Mesulam et al. 2008; Forman et al. 2006; Davies et al. 2005; Hodges et al. 2004; Knopman et al. 2005). It is not possible to estimate quantitatively the extent of under- or overdiagnosis of CS-FTLD syndromes. To resolve both misclassification problems, very large, longitudinal clinical–pathological studies would be required that were free of biases during recruitment that would compromise the estimates. Patients with dementia of any presumed etiology would have to be recruited and followed to death and autopsy confirmation of diagnosis.
- Edad 45-65: total 108; bvFTD:90, SD:3, PNFA:15 Edad 66-75: total 97; bvFTD:75, SD:7, PNFA:15 Edad 76-85: total 21; bvFTD:15, SD:3, PNFA:3 We found that in Brescia county the prevalence of FTLD is higher, accounting for 17.6 cases out of 100,000 inhabitants. It is a common form of dementia at the ages 45–65 (22/100,000 inhabitants), and its prevalence significantly increases at the ages 66– 75 (78/100,000 persons). Further, we confirmed that FTLD diagnosis needs to be considered in the older population, with the prevalence of 54/100,000 inhabitants in patients over 75 years old. It is possible that the very high estimates of prevalence in persons over age 65 years in some studies (Borroni et al. 2010; Garre-Olmo et al. 2010) do not reflect neuropathological FTLD and therefore represent an overdiagnosis of bvFTD. Neuropathological studies typified by the large multicenter study (Rascovsky et al. 2011) simply do not support the contention that most FTLDs occur in persons over age 65. To address the wide divergence of extant prevalence estimates in the younger and older age ranges, we drew on other data. First, we examined the age range of a series of autopsy-proved cases of FTLD drawn from an international consortium of centers with expertise in bvFTD (Rascovsky et al. 2011). The study set included 176 cases, of which approximately 63% had an age of onset between 45 and 64 years, 9.7% an age of onset <45 years, and 27.3% an age of onset >64 years. We also examined a clinical series of 353 patients drawn from three centers that specialized in FTLD disorders (Johnson et al. 2005). In that series, about 30% had onset after age 65 years. Using these two alternate resources together with the prevalence data from the Netherlands (Rosso et al. 2003), we therefore estimated that 10% of CS-FTLD patients were <45 years of age and 30% were over age 65 years of age at onset.
- Two usages of the term ‘Pick’s disease’ have since become commonly, but divergently, applied. Especially in German neurology, Pick’s disease has been used to designate the clinical diagnosis of a frontal dementia, with or without pathologically proven Pick bodies or Pick cells. In the American literature, by contrast, Pick’s disease has been predominantly used as a pathological diagnosis, irrespective of the clinical presentation. (For similar discussions of the history of terminology of non-Alzheimer dementias see also Poeck and Luzzatti, 1988, Hodges et al., 1998, Rossor, 2001). Given this ambiguity, some authors have dropped the term altogether and preferred terms such as frontotemporal degeneration or frontotemporal dementia with or without Pick pathology (Snowden et al., 1996). In acknowledgement of the complex interrelations with other neurodegenerative diseases such as corticobasal degeneration, the term ‘Pick complex’ has now been suggested to stress clinical, pathological, histochemical, and genetic similarities amongst these degenerative conditions (Kertesz, 1997). The importance of these issues is emphasised by the fact that these conditions are not rare: up to a quarter of all degenerative dementias diseases belong to the Pick complex (Kertesz, 1998b). Furthermore, it is worth remarking that this ‘discovery’ is not recent. As early as 1926, Onari and Spatz wrote: We hold the opinion that Pick’s disease does not belong to the extreme rarities, but that it remains often unrecognised by the clinician as well as the anatomist because not enough attention is directed to it. Pick’s disease was defined as a neurodegenerative disorder characterized by severe circumscribed lobar atrophy, marked neuronal loss and gliosis, swollen neurons and Pick bodies. However, the term Pick complex with various neuropathological substrates is also used in clinical research. Presence of globular or spherical tau-positive, argyrophilic (not with Gallyas silver staining) neuronal cytoplasmic inlcusions, called Pick bodies, in the granule cells of the dentate gyrus (DG) and pyramidal neurons of CA1 subregion of the hippocampus, temporal and/or frontal cortex characterize Pick’s disease, also called fronto temporal lobar degeneration (FTLD) with Pick bodies.
- FTLD patients have been shown to be less impaired on measures of memory than AD patients (Beyreuther & Arendt, 2002; Clark & Trojanowski, 2000; Elfgren et al., 1994; Harciarek & Jodzio, 2005; Hodges et al., 1999; Hutchinson & Mathias, 2007; Levy & Chelune, 2007; Mathuranath et al., 2000; Pasquier et al., 2001; Perry & Hodges, 2000; Rascovsky et al., 2002; Walker et al., 2005). Moreover, they have been shown to have better delayed recall (Diehl et al., 2005; Glosser et al., 2002; Gregory et al., 1997; Hodges & Miller, 2001; Hornberger, Piguet, Graham, Nestor, & Hodges, 2010; Lindau et al., 1998; Walker et al., 2005) and recognition (Harciarek & Jodzio, 2005; Mendez et al., 1996). FTLD patients perform better on recognition than recall measures, which may be due to the preserved ability of patients to use cues (intact priming effect) (Kertesz, 2006; Kertesz et al., 2003). Pasquier et al. (2001) showed that AD and bvFTD patients differed in immediate cued recall (encoding) with AD patients performing worse, and with total recall, recognition and learning consistency more preserved in bvFTD. Perhaps the most consistent finding is the relative preservation of episodic memory in FTLD relative to other neurodegenerative patients (Harciarek & Jodzio, 2005; Hutchinson & Mathias, 2007; Kramer et al., 2003; Marra et al., 2007; Perry & Hodges, 2000). However, FTLD patients may perform worse than controls on tests of memory, which some studies have attributed to disruptive executive control processes associated with pathology in prefrontal brain regions leading to impairments in attention and active, organized strategies for encoding and retrieval (Beyreuther & Arendt, 2002; Glosser et al., 2002; Harciarek & Jodzio, 2005; Levy & Chelune, 2007; Lindau et al., 1998; Marra et al., 2007; Pasquier, 1999; Rascovsky et al., 2002).
- Three of the following behavioural/cognitive symptoms (A–F) must be present to meet criteria. Ascertainment requires that symptoms be persistent or recurrent, rather than single or rare events. As a general guideline ‘early’ refers to symptom presentation within the first 3 years.
- The study found the FTDC criteria to have good sensitivity and specificity, indicating that they are effective in distinguishing between FTLD and other pathologies during life. Predictably, there was a tradeoff between sensitivity and specificity for “probable” compared with “possible” FTD criteria, reflecting the fact that although frontotemporal changes on neuroimaging increase specificity of diagnosis of FTD, they may not invariably be present in early-stage disease. The cohort encompassed the range of FTLD pathologies, confirming that the criteria are sensitive to bvFTD associated with tau, TDP-43, and fused in sarcoma pathologies. Analysis of individual behavioral features showed differences in relative strength. Whereas emotional and dietary changes have high specificity for bvFTD, they are not invariably present, thus have proportionally lower sensitivity. By contrast, the prominence of executive over other cognitive deficits is highly sensitive. The latter finding underlines the importance of neuropsychological assessment in the evaluation of patients with FTD. Examination of false-negative and false-positive cases is instructive. Two patients, who were diagnosed clinically with FTD at their first assessment and had FTLD pathology, did not meet FTDC criteria because they endorsed only 2 behavioral/cognitive features: apathy and executive impairment. This finding exemplifies the point that criteria provide a valuable adjunct to but are not a substitute for clinical experience. The majority of false-positive “possible bvFTD” cases had AD pathology. It is recognized that AD may occasionally present as a circumscribed frontal lobe syndrome and masquerade as bvFTD.12–14. The false- positive cases included 3 such patients, 1 of whom fulfilled criteria for probable bvFTD on the grounds of circumscribed frontal atrophy on imaging. However, other false-positive cases showed additional features of memory impairment and/or mild visuospatial impairment, which are typical of AD. Indeed, those patients had been diagnosed with AD in life. The relaxation of exclusion features in the FTDC criteria compared with the 1998 criteria stems from increased awareness of the potential variability in clinical phenotype: the presence of amnesia or “parietal” features does not necessarily rule out FTLD pathology 8,10,15. Indeed, one patient in this study had amnesia but the pathology was corticobasal degeneration together with hippocampal sclerosis. Moreover, executive impairments may secondarily compromise performance on memory and perceptuospatial tests 16. Nevertheless, the present findings raise a note of caution: relaxation of exclusion criteria, particularly in relation to the presence of spatial impairment, might inadvertently increase false-positive cases. False positivity in DLB is worthy of comment. The presence of fluctuations in mental state, parkinsonism, and hallucinations normally allows differentiation of DLB from bvFTD. However, such features are not invariably present. Moreover, delusions and hallucinations may occur in a subset of patients with bvFTD, particularly those with C9ORF72 repeat expansions.17 Furthermore, the tangential line of thought typical of patients with DLB may be difficult to distinguish from the unmonitored utterances of some patients with bvFTD. Indeed, it has been surmised that there may be a subgroup of DLB patients that mimics bvFTD 18,19. In the present false-positive DLB case, mild perceptuospatial and motor features were present and the clinical diagnosis was DLB. However, relaxation of exclusion criteria meant that the patient fulfilled bvFTD criteria. The present study yielded sensitivity levels (95% and 85% for possible and probable bvFTD, respectively) that are higher than the 86% and 76% figures reported in the multicenter FTDC criteria study.11 In that study, it was noted that patients who failed to meet criteria were older and had more atypical presentations with memory impairment than other patients. The present cohort is remarkably well matched to that of the earlier study11 in terms of mean age at onset, assessment, and death. However, the SD is slightly smaller, raising the possibility that the present cohort contained fewer “outliers”of older, atypical cases. In the present study, a high rate of positive family history was recorded in both FTLD and non-FTLD groups. A positive family history was defined as the presence of dementia in 1 first-degree relative. Therefore, a positive family history may not necessarily imply an autosomal dominant pattern of inheritance in all these cases. A strength of the current study is that case material was all drawn from a single center. Patients had under gone a relatively uniform diagnostic assessment, which included a behavioral history tapping the range of behaviors associated with bvFTD. Thus, data pertaining to FTLD and non-FTLD cases are directly comparable. Ratings were performed blind both to clinical and pathologic diagnosis by “naive” raters who had no personal knowledge of the patients. An independent pilot study, involving ratings by 5 authors, served as training in the rating process and helped to establish reporting consistency. The study also has limitations. The cohort was biased toward younger-onset dementias, so may not be representative of dementias as a whole. In particular, the findings may not generalize to patients with an older age at onset. Arguably, early- onset dementias are more likely to be confused with FTD, so the comparison of “matched” FTLD and non-FTLD samples is appropriate. However, it is possible that the present cohort does not encompass the range of phenotypic presentations of bvFTD, including older “atypical” bvFTD cases. Very few patients with psychiatric or vascular disease, which can mimic bvFTD, are represented in this study. Behavioral changes in vascular dementia show greater overlap with those of bvFTD, than occurs in AD20. Such changes include alterations in affect and diet. Indeed, 2 of the 3 vascular cases in this study fulfilled FTDC criteria and were diagnosed clinically with FTD. Such findings raise the possibility that specificity of the bvFTD criteria may be overestimated. Future studies should include larger numbers of patients with vascular dementia in their cohorts. There are, conversely, also grounds for assuming that specificity may be underestimated. The study adopted a stringent procedure of treating absence of documentation of a particular behavioral feature as missing data. The majority of such instances occurred, unsurprisingly, in patients with non-FTLD pathology in whom the behavioral feature is likely to be absent. There is a need for prospective studies of sensitivity and specificity to minimize the biases caused by missing data. The present study excluded patients presenting with progressive aphasia. This was important, both to allow direct comparisons with the earlier FTDC study11 and to avoid artificially diluting sensitivity ratings due to cases who a priori would not be expected to meet FTDC criteria. Nevertheless, not all patients exhibit “pure” clinical syndromes of behavioral or language impairment. It would be valuable to ascertain the proportion of patients with progressive aphasia presentations who also fulfill criteria for FTDC. The study, for parallel reasons, excluded patients presenting with extrapyramidal syndromes of progressive supranuclear palsy and corticobasal syndrome. It is of note that there remained cases of progressive supranuclear palsy and corticobasal degeneration pathology. These cases had behavioral/cognitive rather than motor presentations and fulfilled FTDC criteria. It would be important to know the degree to which prototypical progressive supranuclear palsy and corticobasal syndromes might also fulfill behavioral/cognitive criteria for bvFTD. In conclusion, the FTDC criteria for bvFTD show encouragingly high sensitivity and specificity in an autopsy-confirmed cohort of predominantly early- onset dementia patients. Caution should be exercised in the attribution of a bvFTD diagnosis in patients with visuospatial impairment because of the risk of false-positive errors. There is a need for prospective studies involving a wider range of disorders, including vascular disease. The criteria provide the potential to explore the relationship between the distinct syndromes associated with FTLD pathologies
- In substantia nigra it is cytoplasmic, round, eosinophilic with clear halo. In cortex less distinct appearance, best visualized with alpha-synuclein immunohistochemistry
- A staging system, based on the number and location of LBs, with a caudal to rostral six-stage progression has been proposed for sporadic PD (Braak et al.,2003). The first two stages, with LB pathology involving medulla oblongata and pontine tegmentum, are considered asymptomatic or pre symptomatic and may explain the early non-motorsymptoms (autonomic ando lfactory). Stages 3 and 4, with extension of LB pathology to mid brain and basal prosencephalon and mesocortex, have been correlated to clinical symptomatic stages. The terminal stages 5 and 6, characterized by widespread neocortical LB degeneration, are correlated with significant cognitive decline associated with severe parkinsonism (Hurtigetal.,2000). Although there is an acceptable correlation between pathological findings and clinical data in this staging system, mainly in a subgroup with early onset and prolonged duration (Hallidayetal.,2008), recent studies revealed exceptions to the general order of progression suggested by Braak and colleagues (Jellinger,2008; Parkkinen et al.,2008; Dickson etal.,2009; Kalaitzakisetal.,2009). Another interesting observation from a number of recent clinico-pathological studies that assessed the progression of pathology in subtypes of PD is that in patients with non-tremor-dominant and postural instability and gait dominant clinical pictures there are significantly more cortical LBs and amyloid β plaques compared with tremor dominant or younger onset patients (Selikhova et al.,2009;Halliday et al.,2011). Furthermore, PD patients with dementia have higher amounts of cortical αSyn pathology as compared to those without dementia and a correlation between its severity and AD pathology is also present in such patients (Hallidayetal.,2011).
- There is no“gold standard” for the pathological diagnosis of DLB or PDD.The hall mark pathologyis α-synuclein (αSyn) in form of LBs (both classical and cortical types) and LN. Classical LBs are easily recognizable by standard histological methods as large, spherical, highly eosinophilic intracytoplasmatic inclusions with a clear halo in the dopaminergic neurons of substantia nigra and the locus coeruleus (McKeithetal.,1996; Kövarietal.,2009). Cortical LBs are seen in limbic and neocortical regions,predominantly in the small neurons of deep layers of the cortex. Because of their small size they are easily identified using immunohistochemistry with α Syn antibodies (Kövarietal.,2009). LN are curvilinear or dot-like processes that are found in regions with the highest density of LBs, such as limbic cortex and amygdala(Saitoetal.,2003; Dickson, 2010). Inspite of being the hallmark of DLB and PD, LBs they can be detected in the amygdala in up to 50 % of patients with clinically and pathologically confirmed AD (Hamilton,2000) and in up to 10 % of neurologically normal elderly individuals over age of 60 years (Gibb andLees,1998). α-synuclein is a small, presynaptic protein without a well-defined function. Some data implicate the misfolding or aggregation of αSyn in the disease pathogenesis, but the mechanisms that underlie thea berrant functions of αsynuclein and how these impacts on disease pathogenes is remain poorly understood.
- Objective: To investigate the prevalence, incidence, risk factors, and concomitants of Parkinson disease (PD)– associated psychosis (PDP) in a population-based prevalent cohort. Design: Prospective longitudinal cohort study. Setting: Community-based study in southwestern Norway. Participants: Two hundred thirty community-based PD patients were followed up prospectively for 12 years. Reassessments were conducted at 4 and 8 years and then annually. Main Outcome Measures: Severity of PDP was measured by the Unified Parkinson Disease Rating Scale thought disorder (UPDRS-TD) item. Patients with a UPDRS-TD score of 2 or more or those taking antipsychotic drugs owing to psychotic symptoms were categorized at each visit as having PDP. Generalized estimating equations were applied to investigate baseline risk factors for incident PDP and clinical and demographic concomitants of PDP during 12 years. Results: By study’s end, 137 patients (60%) had developed hallucinations or delusions. The incidence rate of PDP was 79.7 per 1000 person-years. Higher age at onset, higher baseline levodopa-equivalent doses, probable rapid eye movement (REM) sleep behavior disorder at baseline, and follow-up time were independent risk factors of incident PDP. Significant concomitant features of patients with PDP during the 12-year study period were low activities of daily living function (UPDRS II), dementia, high levodopa equivalent dose, and probable REM sleep behavior disorder. Conclusions: Psychotic symptoms affect most patients with PD, with increased risk in those with higher age at onset, need for high doses of dopaminergic drugs, and probable REM sleep behavior disorder. This risk factor pattern and the observed associations with increased disability and dementia place PDP within a symptom complex signaling a malignant disease course.
- Distribution of psychotic symptoms in 116 consecutive PD outpatients. Psychotic symptoms include hallucinations and delusions (white bars) and minor phenomena (gray bars). The proportion of patients with psychosis (black bars) is shown, based on the usual definitions (hallucinations or delusions) and the new NINDS-NIMH criteria (hallucinations, delusions, sense of presence, or visual illusions). Values are given in percentages. The distribution of psychotic symptoms in this study was unexpected, non visual hallucinations being about twice as frequent as visual hallucinations. Although auditory hallucinations are mentioned in some studies, with prevalence rates of between 0% and 22%, the frequency of hallucinations in other sensory modalities has rarely been systematically studied. As suggested by previous studies, tactile and olfactory hallucinations are not infrequent. In a recent questionnaire-based study, 31 of 70 PD patients had hallucinations, including 24 patients (34%) with visual hallucinations, and 16 patients (23%) with non visual hallucinations. Focusing on new-onset hallucinations, Goetz et al. found that older patients were more likely to have non visual or mixed hallucinations than purely VH, suggesting that age may influence the distribution of the types of hallucinations. The high prevalence of non visual hallucinations confirms that the use of detailed questionnaires is mandatory to capture the whole spectrum of hallucinatory symptoms. Another important implication of our findings is that explanatory models must integrate the polymodal nature of PDAP (Parkinson’s Disease Associated Psychosis), whereas previous models have focused on visual hallucinations. Minor phenomena were present in 45% of our patients, compared to 25%,17%,13 and 72% of patients enrolled in prospective cross-sectional studies performed in movement disorder clinics. This discrepancy may be due to differences in the study populations, in the questionnaires, and in the time frame chosen to assess PDAP, which ranged from one to three months prior to the date of evaluation. NINDS-NIMH diagnostic criteria for PD-associated psychosis Characteristic symptoms A. Presence of at least one of the following symptoms: Illusions False sense of presence Hallucinations Delusions B. Primary diagnosis UK Brain Bank criteria for PD C. Chronology of the onset of symptoms of psychosis The symptoms in Criterion A occur after the onset of PD D. Duration The symptom(s) in Criterion A are recurrent or continuous for 1 month E. Exclusion of other causes The symptoms in criterion A are not better accounted for by another cause of parkinsonism such as dementia with Lewy bodies, psychiatric disorders (. . .), or a general medical condition including delirium
- El ACE evalúa seis dominios cognitivos. La puntuación máxima obtenible es 100: orientación [10], atención [8], memoria [35], fluencia verbal [14], lenguaje [28] y habilidades visuoespaciales. A su vez, permite calcular los 30 puntos del MMSE, ya que se incluyen en el cuestionario. Si comparamos ambas pruebas, mientras el MMSE asigna 3/30 puntos a la función memoria, el ACE le asigna 35/100, lo que permite evaluar el aprendizaje serial. También agrega el examen de la fluencia verbal y amplía el del lenguaje: suma 10 objetos más a la prueba de denominación, evalúa así más profundamente la lectura de palabras e incluye una prueba de comprensión más exigente. Con respecto a las funciones visuoespaciales, además de los pentágonos cruzados del MMSE, se pide al paciente el dibujo de un cubo y de un reloj. En la adaptación peruana la prueba de aprendizaje y recuerdo del nombre y la dirección fueron cambiadas por Juan Quispe, Avenida Brasil 420, Breña y Lima; y se mantuvo el número de palabras utilizadas; en la prueba de memoria semántica se realizó una adaptación cultural (Presidente del Perú, alcalde de Lima, presidente anterior y ministro de economía); en la prueba de repetición de frases también se realizó otra adaptación cultural (la mazamorra morada tiene duraznos y guindones). Finalmente, en la evaluación de las funciones visuoespaciales se solicitó que las agujas del reloj indiquen las 11:10.
- Se muestra el porcentaje de pacientes en cada grupo que quedaron por encima y por debajo de cada uno de estos puntos de corte, demostrando que ningún paciente con diagnóstico de demencia puntuó por encima del punto de corte del ACE, mientras que un relativamente alto número de pacientes con DFT puntuaron por encima del punto de corte del MMSE para alta educación.
- Del ACE puede extraerse un coeficiente denominado VLOM, (fluidez verbal + lenguaje) / (orientación + recuerdo diferido) diseñado para orientar la discriminación entre la DTA y DFT. Con respecto al coeficiente VLOM, nuestros resultados son similares a aquellos de la publicación de la validación Argentina (12). Si bien el VLOM puede diferenciar DTA de DFT en la presente muestra, debe tenerse en cuenta que no brinda información sobre la naturaleza de esta diferencia entre cuadros de demencia. Por lo tanto, es conveniente complementar el ACE con una herramienta de tamizaje como el INECO Frontal Screening (22) que aporte información acerca del funcionamiento ejecutivo diferencial. De hecho, el INECO Frontal Screening, ha demostrado una muy superior capacidad para detectar déficits ejecutivos que otra herramienta de screening frontal ampliamente utilizada: el Frontal Assessment Battery (FAB) (23). Evidencia de la utilidad limitada del VLOM es la falta de diferencia significativa que se observa entre los grupos en el subdominio de atención en el presente estudio. Asimismo, se aprecia que la diferencia de desempeño en la prueba de fluencia verbal, clásicamente interpretada como una medida de funcionamiento ejecutivo, no es tan marcada como en el resto de los subdominios. En la presente investigación, las diferencias más importantes entre los grupos se registraron en orientación, memoria, atención, fluencia verbal, lenguaje, y habilidades visuoespaciales. El ACE puede realizarse en un tiempo breve (entre 15 y 20 min). Comparado con el MMSE, brinda más información en memoria, denominación, funciones visuoespaciales, e incorpora además la medición de funciones ejecutivas (p. ej., fluencia verbal, prueba del reloj). Al ACE contiene en su estructura al MMSE, lo que permite que se pueda tomar en pacientes cuyas evoluciones se realizaban con ese elemento de screening, o en pacientes muy deteriorados. Si bien las muestras se homogeneizan en cuanto a edad y años de educación, se debe destacar y advertir que la población estudiada tiene como característica una escolaridad promedio de 12 años. Dicho nivel de escolaridad no es representativo de toda la población Peruana: los puntos de corte deben tomarse cuidadosamente, dado que, si bien la puntuación total del ACE no depende del sexo ni de la edad, sí lo hace con respecto a los años de educación. Para realizar una interpretación adecuada de los valores del ACE, son esenciales puntos de corte estratificados por educación.
- 115 individuos seleccionados de forma abierta que acudieron a la unidad de diagnóstico de deterioro cognitivo y prevención de demencia de la clínica Internacional entre Julio del 2011 y Julio del 2013. Se estudiaron tres grupos: 46 controles, 35 con diagnóstico de probable EA (estadio leve-moderado, según puntaje del Clinical Dementia Rating-CDR), y 34 con diagnóstico de probable DFT. A cutoff score of 23.5 points (out of 30) on the IFS was associated with a sensitivity of 97.1%, CI = [89.9, 99.9], and a specificity of 97.9%, CI = [88.9, 99.9], for the detection of dementia (both AD and bvFTD). Regarding the FAB, a cutoff score of 14.5 (out of 18) showed a specificity of 81.1%, CI = [69.9, 89.5] and a sensitivity of 97.9%, CI = [88.3, 99.9]. As shown by Figure 1, the discriminatory accuracy (patients with dementia vs. healthy controls) of the IFS (AuC = 0.99, SE = 0.001) was superior to that of the FAB (AuC = .95, SE = 0.01), and this difference was statistically significant (z = 1.84, p <0.05).
- In comparing the capacity to discriminate between types of dementia (AD vs. FTD), the IFS showed a sensitivity of 94.12%, CI = [80.3, 99.2] and specificity of 94.2%, CI = [80.8, 99.3], using a cutoff score of 17.5 points. On the contrary, a 13-point cutoff score on the FAB showed a sensitivity of 82.3%, CI = [65.4, 93.2], but a low specificity of 48.5%, CI = [31.3, 66.1]. Again, the IFS showed superior discriminatory accuracy (AuC = 0.98, SE = 0.009) than the FAB (AuC = 0.73, SE = 0.05), and this difference was statistically significant (z = 5.57, p < 0.00001).